Dosing and uses of Fragmin (dalteparin)
Adult dosage forms and strengths
injectable solution
- 10,000 International Units/mL
- 25,000 International Units/mL
prefilled syringe
- 2500 International Units/0.2mL
- 5000 International Units/0.2mL
- 7500 International Units/0.3mL
Extended VTE Treatment in Patients with Cancer
200 units IU/kg SC qDay for 30 days, THEn
Months 2-6: 150 units/kg SC qDay
Not to exceed 18,000 units daily
Treatment Duration: 5-10 days usuaL
Severe Mobility Restriction: 5000 units SC qDay
Thrombocytopenia: Dose Reduction
- Plts 50,000-100,000/mm³: Reduce daily dose by 2500 units until 100,000/mm³
- Plts <50,000/mm³, discontinue until >50,000/mm³
Renal Impairment, Severe: Dose Reduction
- CrCl < 30 mL/min: Monitor anti-Xa level to determine appropriate dose
Deep Vein Thrombosis Prophylaxis
Hip Replacement
- PostOp Start
- 2500 units SC 4-8 hr postsurgery, THEREAFTER 5000 units qDay
- PreOp Start
- On day of surgery: 2500 IU SC within 2 hours presurgery, THEN 2500 units SC 4-8 hr postsurgery, THEREAFTER 5000 units SC qDay (administration: At least 6 hr between first post-op dose & Post-op Day 1 dose)
- Evening before Surgery: 5000 units SC 10-14 hr presurgery, THEN 5000 units SC 4-8 hr postsurgery, THEREAFTER 5000 units SC qDay
Abdominal Surgery
- 2500 IU SC 1-2 hr preop, THEREAFTER 2500 units SC qDay
- High risk of thromboembolic complications (eg, malignancy): 5000 units SC evening before surgery, THEN 5000 units qDay (first dose may be evenly split in a preop & postop dose)
Unstable Angina & Non-Q-Wave MI
120 IU/kg SC q12hr for 5-8 days (concurrent with aspirin 75-165 mg qDay)
Not to exceed 10,000 units/dose or 18,000 units/day
Treatment Duration: Continue until patient stabilized; 5-10 days usuaL
Anticoagulation Therapy (Off-label)
200 IU/kg SC qDay or 100 units/kg SC q12hr
Other Indications & Uses
Symptomatic venous thromboembolism (DVT/PE) treatment to reduce recurrence in patients with cancer
Off-label: Treatment of thromboembolism during pregnancy, DVT prophylaxis during knee replacement surgery, neurosurgery, trauma, burns, pediatric
Pediatric dosage forms and strengths
Safety & efficacy not established
Geriatric dosage forms and strengths
Extended VTE Treatment in Patients with Cancer
200 units/kg SC qDay for 30 days, THEn
Months 2-6: 150 units/kg SC qDay
Not to exceed 18,000 units daily
Treatment Duration: 5-10 days usuaL
Severe Mobility Restriction: 5000 units SC qDay
Unstable Angina & Non-Q-Wave MI
120 IU/kg SC q12hr for 5-8 days (concurrent with aspirin 75-165 mg qDay)
Not to exceed 10,000 units/dose or 18,000 units/day
Treatment Duration: Continue until patient stabilized; 5-10 days usuaL
Deep Vein Thrombosis Prophylaxis
Hip Replacement
PostOp Start: 2500 units SC 4-8 hr postsurgery, THEREAFTER 5000 units qDay
PreOp Start: On day of surgery: 2500 IU SC within 2 hours presurgery, THEn
2500 units SC 4-8 hr postsurgery, THEREAFTER 5000 units SC qDay (administration: At least 6 hr between first post-op dose & Post-op Day 1 dose)
Evening before surgery: 5000 units SC 10-14 hr presurgery, THEN 5000 units SC 4-8 hr postsurgery, THEREAFTER 5000 units SC qDay
Abdominal Surgery
2500 IU SC 1-2 hr preop, THEREAFTER 2500 units SC qDay
High risk of thromboembolic complications (eg, malignancy): 5000 units SC evening before surgery, THEN 5000 units qDay (first dose may be evenly split in a preop & postop dose)
Fragmin (dalteparin) adverse (side) effects
1-10%
Injection site hematoma (7-35%)
Thrombocytopenia (10.9-13.6%, patients with cancer )
Injection site pain (4.5-12%)
Major hemorrhage (up to 4.6%)
Increased liver function test (up to 4.3%)
Wound hematoma
Hematuria
Frequency not defined
Epidural hematoma
Spinal hematoma
Hemorrhagic cerebral infarction
Intracranial hemorrhage
Intrauterine subdural hemorrhage
Thrombocytopenia (<1%, non-cancer indications)
Anaphylactoid reaction (rare)
Warnings
Black box warnings
Epidural or spinal hematomas may occur in patients anticoagulated with LMWH or heparinoids who receive neuraxial (epidural/spinal) anesthesia or spinal puncture
These hematomas may result in long-term or permanent paralysis
Patients should be frequently monitored for signs and symptoms of neurologic impairment; if neurological compromise noted, urgent treatment necessary
Optimal timing between the administration of dalteparin and neuraxial procedures is not known
Physicians should consider the benefits versus risk before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis
Factors increasing risk of epidural or spinal hematomas
- Indwelling epidural catheters
- Concomitant use of other drugs that affect hemostasis (eg, NSAIDs, platelet inhibitors, other anticoagulants)
- History of traumatic or repeated epidural or spinal punctures
- History of spinal deformity or spinal surgery
Contraindications
Hypersensitivity to dalteparin, heparin or pork products
Active major bleeding, thrombocytopenia associated with antiplatelet antibodies
History of heparin induced thrombocytopenia or heparin induced thrombocytopenia with thrombosis
As a treatment for unstable angina and non-Q-wave MI, in patients undergoing epidural/neuraxial anesthesia
For prolonged VTE prophylaxis, in patients undergoing epidural/neuraxial anesthesia
Patients that have undergone epidural neuraxial anesthesia
Cautions
Risk of epidural/spinal hematoma if used in patients getting epidural/spinal anesthesia which may result in paralysis
Use caution in conditions with increased risk of hemorrhage, hemorrhagic diathesis, severe uncontrolled HTN, severe hepatic/renal impairment, retinopathy, thrombocytopenia, bacterial endocarditis, GI ulcer, hemorrhagic stroke, recent brain, spinal or ophthalmologic surgery
Periodic blood counts recommended
History of heparin-induced thrombocytopenia
Do not give Im
Can't be used interchangeably with other LMW heparins
Multidose vials contain benzyl alcohol as preservative (associated with potentially fatal "Gasping Syndrome" in preemies)
Therapy may enhance risk of bleeding in patients with thrombocytopenia or platelet defects; severe liver or kidney insufficiency, hypertensive or diabetic retinopathy, and recent gastrointestinal bleeding; bleeding can occur at any site during therapy; monitor thrombocytopenia of any degree closely
If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae
For patients with creatinine clearance <30mL/min, elimination of dalteparin may be prolonged; consider doubling the timing of removal of a catheter, at least 24 hr for lower prescribed dose of dalteparin (2500 IU or 5000 IU once daily) and at least 48 hr for higher dose (200 IU/kg once daily, 120 IU/kg twice daily)
Although specific recommendation for timing of a subsequent dose after catheter removal is unknown, consider delaying this next dose for at least four hours, based on a benefit-risk assessment considering both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors
Pregnancy and lactation
Pregnancy category: B
Lactation: Enters breast milk; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Fragmin (dalteparin)
Mechanism of action
LMW heparin with antithrombotic properties; enhances inhibition of Factor Xa & thrombin by antithrombin, minimal effect on APTt
Pharmacokinetics
Half-Life: 3-5 hr
Onset of action: 1-2 hr (anti Xa activity)
Peak plasma time: 4 hr
Duration: >12hr
Peak plasma concentration: 0.19 IU/mL (2500 IU dose)
Protein binding: Low
Bioavailability: 81-93%
Vd: 40-60 mL/kg
Excretion: Urine
Clearance: 15-25 mL/hr/kg (dose-dependent)
